CN102160853A - Vinpocetine injection and preparation method thereof - Google Patents
Vinpocetine injection and preparation method thereof Download PDFInfo
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- CN102160853A CN102160853A CN 201110036104 CN201110036104A CN102160853A CN 102160853 A CN102160853 A CN 102160853A CN 201110036104 CN201110036104 CN 201110036104 CN 201110036104 A CN201110036104 A CN 201110036104A CN 102160853 A CN102160853 A CN 102160853A
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Abstract
The invention relates to a vinpocetine injection and a preparation method thereof. The vinpocetine injection is mainly prepared from vinpocetine, a cosolvent and a physical stabilizer and contains a pH regulator and a metal ion chelator. The pH range is close to the neutrality, the irritation of the vinpocetine injection is small, the stability of the vinpocetine injection is good, and antioxidants and vascular irritation regulators do not need to be added. The invention has the beneficial effects that the chemical stability of the vinpocetine injection is better, the vinpocetine injection can be stored at room temperature, the foreign matter inspection result meets the rules, and the safety of the vinpocetine injection is high.
Description
Technical field:
The present invention relates to a kind of vinpocetine injection and preparation method thereof, particularly a kind of pH value scope is closely neutral, stability of drug products is good, blood vessel irritation is little, do not need with antioxidant and blood vessel irritation regulator, make the physics stabilizing agent without sorbitol, medicine is fit to the preparation method of the vinpocetine injection of diabetes patient's use.
Background technology:
Vinpocetine is a kind of indoles alkaloid, is at first succeeded in developing by Hungary GedeonRichter company in 1978, and mandate how tame in the world drugmaker in back produces, and also uses as conventional medicine in European and American countries and Japan's listing at present.June 29 calendar year 2001, National Drug Administration was with the accurate word X20010467 of traditional Chinese medicines code at home; the vinpocetine injection of approval Zhengzhou Hong Hui pharmaceutical Co. Ltd (the existing sharp pharmacy of Zhengzhou antelope) is produced without competition at home as four kind new medicines; injection in 2002 " moistens smooth " to go on the market at home; at present domestic have only the sharp pharmacy of antelope one family to produce the small-volume injection of vinpocetine, and the preparation method patent protection is arranged.
There is following defective in commercially available vinpocetine injection: the pH value scope is closely acid, causes the medicine blood vessel irritation strong, uses benzyl alcohol as the blood vessel irritation regulator, and large usage quantity, and hemolytic risk is arranged; The pH value scope is closely acid, causes stability of drug products poor, needs to use antioxidant as chemical stabilizer, and drug safety is poor; Make the physics stabilizing agent with sorbitol, medicine is not suitable for the diabetes patient and uses.
Summary of the invention:
The problem to be solved in the present invention mainly is: the vinpocetine raw material is white or flaxen crystalline powder; Easily molten in chloroform, glacial acetic acid, molten in the general Methanamide part omitted of diformazan, soluble,very slightly in methanol, ethanol, insoluble in water.According to raw material properties, adopt the organic acid hydrotropy, add the physics stabilizing agent behind the material dissolution, after strengthening the physical stability of medicine, adjust back pH value again, strengthen the chemical stability of medicine near neutral, reduce the zest of medicine, do not need with antioxidant and blood vessel irritation regulator; Make the physics stabilizing agent without sorbitol, medicine is fit to the diabetes patient to be used.
Prescription:
Method for making:
Get 50% water for injection, add metal ion chelation agent, stir and make dissolving; Add vinpocetine, add cosolvent, stirring is dissolved raw material fully; Add the physics stabilizing agent, stir; Slowly add the pH value regulator, the limit edged stirs, and regulates pH value near neutral; Add to the full amount of water for injection, stir.Add 0.02% active carbon, left standstill filtering decarbonization 20 minutes; Detect character (colourless clear liquid), pH value (4.0～6.0), the content (97%～103%) of medicinal liquid qualified after, filter (0.45 μ m, 0.22 μ m) inflated with nitrogen embedding, 115 ℃ of pressure sterilizings 30 minutes, lamp inspection, packing.
The present invention relates to a kind of vinpocetine injection, mainly, wherein contain pH value regulator, metal ion chelation agent by constituting by vinpocetine, cosolvent, physically stable agent; The pH value scope is near neutral, and the zest of medicine is little, and the good stability of medicine need not add antioxidant and vascular stimulation regulator.
The present invention relates to a kind of manufacture method of vinpocetine injection, get 50% water for injection, add metal ion chelation agent, stir and make dissolving; Add vinpocetine, add cosolvent, stirring is dissolved raw material fully; Add the physics stabilizing agent, stir; Slowly add the pH value regulator, the limit edged stirs, and regulates pH value to 4.0～6.0; Add to the full amount of water for injection, stir, the ratio of principal agent and each adjuvant ratio by weight is: vinpocetine 5～10 weight portions, cosolvent 5～10 weight portions, physically stable agent 1000～5000 weight portions, pH value regulator 5～30 weight portions, metal ion chelation agent 1～10 weight portion, water for injection adds to 10000 weight portions.
A kind of vinpocetine injection: described cosolvent is any in tartaric acid, citric acid, the maleic acid, or any combination is used simultaneously, described physically stable agent is any in propylene glycol, glycerol, the xylitol, or any combination is used simultaneously, described pH value regulator is any in sodium bicarbonate, sodium carbonate, the sodium hydroxide, or any combination is used simultaneously, described pH value scope is 4.0～6.0, described metal ion chelation agent is any in disodium edetate, the calcium disodium edetate, or any combination is used simultaneously.
Beneficial effect of the present invention:
1, hot test:
Sample thief is put into 60 ℃ of calorstats, sampling in the 5th day, the 10th day, detects character, pH value, visible foreign matters, content, related substance respectively.
The result shows, destroys through 10 days high temperature, and the detection index of sample does not have significant change, and the chemical stability of sample is better, can room temperature preservation.
2, freezing-thawing test:
Sample thief is put into the circulating freezing resistance proof box, preserves 48 hours at-20 ℃, is warmed up to 40 ℃ and preserves 48 hours, carries out circulating freezing resistance 3 times, the character of sample for reference, pH value, visible foreign matters.
The result shows that behind the freeze-thaw cycle, the medicine physical stability is fine, does not separate out crystallization, and the visible foreign matters check result is up to specification.
3, local irritation test
Make sample with manufacture method of the present invention, do blood vessel irritation test at White Rabbit auricular vein place, the result does not have tangible zest, medicine safe.
Description of drawings
Fig. 1 is a manufacturing flow chart of the present invention
The specific embodiment:
Example one:
Prescription:
Method for making:
Get 50% water for injection as shown in Figure 1, add calcium disodium edetate, stir and make dissolving; Add vinpocetine, add tartaric acid, stirring is dissolved raw material fully; Add propylene glycol, stir; Slowly add 10% sodium bicarbonate solution, the limit edged stirs, and regulates pH value to 4.0～6.0; Add to the full amount of water for injection, stir, add 0.02% active carbon, left standstill filtering decarbonization 20 minutes; Detect character (colourless clear liquid), pH value (4.0～6.0), the content (97%～103%) of medicinal liquid qualified after, filter (0.45 μ m, 0.22 μ m) inflated with nitrogen embedding, 115 ℃ of pressure sterilizings 30 minutes, lamp inspection, packing.
Example two:
Prescription:
Method for making:
Get 50% water for injection, add calcium disodium edetate, stir and make dissolving; Add vinpocetine, add citric acid, stirring is dissolved raw material fully; Add propylene glycol, stir; Slowly add 10% sodium bicarbonate solution, the limit edged stirs, and regulates pH value to 4.0～6.0; Add to the full amount of water for injection, stir, add 0.02% active carbon, left standstill filtering decarbonization 20 minutes; Detect character (colourless clear liquid), pH value (4.0～6.0), the content (97%～103%) of medicinal liquid qualified after, filter (0.45 μ m, 0.22 μ m) inflated with nitrogen embedding, 115 ℃ of pressure sterilizings 30 minutes, lamp inspection, packing.
Example three:
Prescription:
Method for making:
Get 50% water for injection, add calcium disodium edetate, stir and make dissolving; Add vinpocetine, add tartaric acid, stirring is dissolved raw material fully; Add glycerol, stir; Slowly add 10% sodium bicarbonate solution, the limit edged stirs, and regulates pH value to 4.0～6.0; Add to the full amount of water for injection, stir, add 0.02% active carbon, left standstill filtering decarbonization 20 minutes; Detect character (colourless clear liquid), pH value (4.0～6.0), the content (97%～103%) of medicinal liquid qualified after, filter (0.45 μ m, 0.22 μ m) inflated with nitrogen embedding, 115 ℃ of pressure sterilizings 30 minutes, lamp inspection, packing.
Example four:
Prescription:
Method for making:
Get 50% water for injection, add disodium edetate, stir and make dissolving; Add vinpocetine, add tartaric acid, stirring is dissolved raw material fully; Add glycerol, stir; Slowly add 10% sodium carbonate liquor, the limit edged stirs, and regulates pH value to 4.0～6.0; Add to the full amount of water for injection, stir, add 0.02% active carbon, left standstill filtering decarbonization 20 minutes; Detect character (colourless clear liquid), pH value (4.0～6.0), the content (97%～103%) of medicinal liquid qualified after, filter (0.45 μ m, 0.22 μ m) inflated with nitrogen embedding, 115 ℃ of pressure sterilizings 30 minutes, lamp inspection, packing.
Claims (8)
1. a vinpocetine injection mainly is to be made of vinpocetine, cosolvent, physically stable agent, is primarily characterized in that: wherein contain pH value regulator, metal ion chelation agent; The pH value scope is near neutral, and the zest of medicine is little, and the good stability of medicine need not add antioxidant and vascular stimulation regulator.
2. the manufacture method of a vinpocetine injection is primarily characterized in that: get 50% water for injection, add metal ion chelation agent, stir and make dissolving; Add vinpocetine, add cosolvent, stirring is dissolved raw material fully; Add the physics stabilizing agent, stir; Slowly add the pH value regulator, the limit edged stirs, and regulates pH value to 4.0～6.0; Add to the full amount of water for injection, stir.
3. a kind of vinpocetine injection according to claim 1, it is characterized in that: the ratio of principal agent and each adjuvant ratio by weight is: vinpocetine 5～10 weight portions, cosolvent 5～10 weight portions, physically stable agent 1000～5000 weight portions, pH value regulator 5～30 weight portions, metal ion chelation agent 1～10 weight portion, water for injection adds to 10000 weight portions.
4. medicaments injection according to claim 1 and 2 is characterized in that: described cosolvent is any in tartaric acid, citric acid, the maleic acid, or any combination is used simultaneously.
5. medicaments injection according to claim 1 and 2 is characterized in that: described physically stable agent is any in propylene glycol, glycerol, the xylitol, or any combination is used simultaneously.
6. medicaments injection according to claim 1 and 2 is characterized in that: described pH value regulator is any in sodium bicarbonate, sodium carbonate, the sodium hydroxide, or any combination is used simultaneously.
7. medicaments injection according to claim 1 and 2 is characterized in that: described pH value scope is 4.0～6.0.
8. medicaments injection according to claim 1 and 2 is characterized in that: described metal ion chelation agent is any in disodium edetate, the calcium disodium edetate, or any combination is used simultaneously.
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| Application Number | Priority Date | Filing Date | Title |
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| CN 201110036104 CN102160853A (en) | 2011-02-11 | 2011-02-11 | Vinpocetine injection and preparation method thereof |
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| CN 201110036104 CN102160853A (en) | 2011-02-11 | 2011-02-11 | Vinpocetine injection and preparation method thereof |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102716125A (en) * | 2011-11-14 | 2012-10-10 | 河南润弘制药股份有限公司 | Vinpocetine composition and preparation method thereof |
| CN102716065A (en) * | 2011-11-14 | 2012-10-10 | 河南润弘制药股份有限公司 | Vinpocetine injection and preparation method thereof |
| CN103202805A (en) * | 2013-03-22 | 2013-07-17 | 东北制药集团股份有限公司 | Vinpocetine-containing pharmaceutical composition for injection and preparation method thereof |
| CN103462888A (en) * | 2013-09-16 | 2013-12-25 | 江苏正大清江制药有限公司 | Substituted beta-cyclodextrin included vinpocetine injection and preparation method thereof |
| CN110179745A (en) * | 2018-07-16 | 2019-08-30 | 北京海浈医药科技有限公司 | A kind of Vinpocetine injection and preparation method thereof |
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| CN101066244A (en) * | 2006-09-28 | 2007-11-07 | 郑州羚锐制药有限公司 | Small volume vincamine injection and its prepn process |
| RU2359669C1 (en) * | 2007-10-17 | 2009-06-27 | Закрытое Акционерное Общество "Канонфарма Продакшн" | Pharmaceutical composition in form of solution for injections, possessing cerebrovasodilating and nootropic activity, and method of its reception |
| CN101791310A (en) * | 2010-02-24 | 2010-08-04 | 王保明 | Vinpocetine medicine composition and preparation method thereof |
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2011
- 2011-02-11 CN CN 201110036104 patent/CN102160853A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101066244A (en) * | 2006-09-28 | 2007-11-07 | 郑州羚锐制药有限公司 | Small volume vincamine injection and its prepn process |
| RU2359669C1 (en) * | 2007-10-17 | 2009-06-27 | Закрытое Акционерное Общество "Канонфарма Продакшн" | Pharmaceutical composition in form of solution for injections, possessing cerebrovasodilating and nootropic activity, and method of its reception |
| CN101791310A (en) * | 2010-02-24 | 2010-08-04 | 王保明 | Vinpocetine medicine composition and preparation method thereof |
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| 《中华中医药杂志》 20101231 张兰华 等 近年来长春西汀临床研究及应用进展 2070-2075页 1-8 第25卷, 第12期 * |
| 《山西临床医药杂志》 20020531 徐涛成 等 木糖醇注射液对糖尿病血糖影响的临床研究 摘要及讨论部分 5 第11卷, 第5期 * |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102716125A (en) * | 2011-11-14 | 2012-10-10 | 河南润弘制药股份有限公司 | Vinpocetine composition and preparation method thereof |
| CN102716065A (en) * | 2011-11-14 | 2012-10-10 | 河南润弘制药股份有限公司 | Vinpocetine injection and preparation method thereof |
| CN102716065B (en) * | 2011-11-14 | 2014-04-16 | 河南润弘制药股份有限公司 | Vinpocetine injection and preparation method thereof |
| CN103202805A (en) * | 2013-03-22 | 2013-07-17 | 东北制药集团股份有限公司 | Vinpocetine-containing pharmaceutical composition for injection and preparation method thereof |
| CN103202805B (en) * | 2013-03-22 | 2015-02-25 | 东北制药集团股份有限公司 | Vinpocetine-containing pharmaceutical composition for injection and preparation method thereof |
| CN103462888A (en) * | 2013-09-16 | 2013-12-25 | 江苏正大清江制药有限公司 | Substituted beta-cyclodextrin included vinpocetine injection and preparation method thereof |
| CN103462888B (en) * | 2013-09-16 | 2016-03-02 | 江苏正大清江制药有限公司 | Vinpocetine injection of a kind of beta-cyclodextrin inclusion compound of replacement and preparation method thereof |
| CN110179745A (en) * | 2018-07-16 | 2019-08-30 | 北京海浈医药科技有限公司 | A kind of Vinpocetine injection and preparation method thereof |
| CN110179745B (en) * | 2018-07-16 | 2021-09-10 | 北京海浈医药科技有限公司 | Vinpocetine injection and preparation method thereof |
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Application publication date: 20110824 |